Changes in the phospholipid catabolism of mitochondria and microsomes during the development of rat liver.
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ABSTRACT:
SUBMITTER: Pollak JK
PROVIDER: S-EPMC1163573 | biostudies-other | 1981 Dec
REPOSITORIES: biostudies-other
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Project description:1. The catabolism of glycine was studied in isolated rat liver mitochondria by measuring release of 14CO2 from [1-14C]-glycine. Incubation of mitochondria in a medium containing 0.5 microM free Ca2+ resulted in an 8-fold increase in the rate of degradation of glycine. Intraperitoneal injection of glucagon (33 or 100 micrograms/100 g body wt.) 25 min before killing of rats also resulted in a 3-fold or 10-fold (depending on dosage) increase in the rate of catabolism of glycine. 2. Both the stimulation by free Ca2+ and that by injection of glucagon in vivo were dependent on phosphate in the incubation medium. This requirement for phosphate was specific, as replacement of phosphate by other permeant anions such as thiocyanate and acetate did not permit the stimulation. The phosphate-dependent stimulation of glycine catabolism by Ca2+ was also evident when mitochondria were incubated in the absence of K+. 3. Mitochondria isolated from rats previously injected with glucagon showed elevated rates of degradation of glycine even in the presence of rotenone, provided that regeneration of NAD+ was affected by providing acetoacetate. 4. Hypo-osmolarity of the medium markedly stimulated the rate of degradation of glycine by mitochondria. Although hypo-osmolarity-induced stimulation of glycine degradation was accompanied by parallel changes in mitochondrial matrix volume, no measurable changes in matrix volume were observed in mitochondria stimulated either by free Ca2+ (0.5 microM) or by injection of glucagon in vivo. Furthermore, Ca2+ stimulated glycine decarboxylation in mitochondria exposed to either hyper-osmolar (410 mosmol) or hypo-osmolar (210 mosmol) conditions. Although hyper-osmolarity decreased and hypo-osmolarity increased matrix volume, stimulation of glycine degradation by Ca2+ was not associated with any further changes in matrix volume. 5. These data demonstrate that the regulation of hepatic glycine oxidation by glucagon and by free Ca2+ is largely independent of changes in mitochondrial matrix volume.
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Project description:Ochratoxin A (OTA), one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), UHPLC-Orbitrap-high resolution mass spectrometry (HRMS) and liquid chromatography-multiple stage mass spectrometry (LC-MS(n)) were utilized to investigate the metabolic profile of OTA in rat liver microsomes. Three conjugated products of OTA corresponding to amino-, phenol- and acyl-glucuronides were identified, and the related structures were confirmed by hydrolysis with ?-glucuronidase. Moreover, OTA methyl ester, OT? and OT?-glucuronide were also found in the reaction solution. Based on these results, an in vitro metabolic pathway of OTA has been proposed for the first time.
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Project description:Chlordane, heptachlor, and their metabolites are chiral persistent organic pollutants that undergo enantiomeric enrichment in the environment. This study investigated the enantioselective metabolism of both chlordane isomers and heptachlor, major components of technical chlordane, by liver microsomes prepared from male rats treated with corn oil (CO) or inducers of CYP2B (PB; phenobarbital) and CYP3A enzymes (DX; dexamethasone), isoforms induced by chlordane treatment. The extent of the metabolism of all three parent compounds was dependent on the microsomal preparation used and followed the rank order PB > DX > CO. The mass balances ranged from 49 to 130% of the parent compound added to the microsomal incubations. Both cis- and trans-chlordane were enantioselectively metabolized to oxychlordane (EF = 0.45-0.89) and 1,2-dichlorochlordene (EF = 0.42-0.90). Heptachlor was metabolized enantioselectively, with heptachlor epoxide B (EF = 0.44-0.54) being the only metabolite. Interestingly, the direction on the enrichment for oxychlordane, 1,2-dichlorochlordene, and heptachlor epoxide differed depending on the microsomal preparation. These findings demonstrate that the direction and extent of the enantioselective metabolism of both chlordane isomers and heptachlor is P450 isoform-dependent and can be modulated by the induction of P450 enzymes.
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Project description:1. Lipogenesis, as measured by the incorporation of (14)C-labelled glucose or acetate into fatty acids in liver slices, is high in foetal and adult rat liver but is low in the liver of the suckling rat, especially with glucose as substrate. 2. The rate of synthesis of non-saponifiable lipids from glucose is about 15 times as great in the liver of the 18-day foetus as in adult liver. Activity in the newborn is negligible. 3. Glucose incorporation into fat is strongly concentration-dependent in liver slices from the adult and 2-week-old rat, but less markedly so in liver slices from the foetus. 4. Changes in the activity of hepatic citrate-cleavage enzyme (ATP-citrate lyase) occur in parallel with the changes in the extent of fatty acid formation, supporting the participation of this enzyme in lipogenesis. However, NADP-malate dehydrogenase, a potential source of reduced nucleotide coenzyme for lipogenesis in the adult, could not be detected in foetal rat liver.
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Project description:Gelsemium is a small genus of flowering plants from the family Loganiaceae comprising five species, three of which, Gelsemium sempervirens (L.) J. St.-Hil., G. elegans Benth and G. rankinii Small, are particularly popular. Compared with other alkaloids from G. elegans, gelsemine, gelsevirine and koumine exhibit equally potent anxiolytic effects and low toxicity. Although the pharmacological activities and metabolism of koumine and gelsemine have been reported in previous studies, the species differences of gelsevirine metabolism have not been well studied. In this study, the metabolism of gelsevirine was investigated by using liver microsomes of humans, pigs, goats and rats by means of HPLC-QqTOF/MS. The results indicated that the metabolism of gelsevirine in liver microsomes had qualitative and quantitative species differences. Based on the results, the possible metabolic pathways of gelsevirine in liver microsomes were proposed. Investigation of the metabolism of gelsevirine will provide a basis for further studies of the in vivo metabolism of this drug.
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Project description:The concentration and composition of phospholipids and mitotic activity in regenerating rat liver were studied. (1) The total amount of liver phospholipid increased approximately linearly during 48h after operation but without change in the relative concentrations of individual phospholipids. (2) The appearance of mitoses 30h after operation was accompanied by an increased incorporation of (32)P into the liver phospholipids. (3) The regenerating livers incorporated a higher percentage of the label into the phosphatidylserine+phosphatidylinositol fraction than those of control rats. The percentage of the label incorporated into phosphatidylethanolamine in these livers increased but decreased in the phosphatidylcholine.
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Project description:Genistein is a natural phytoestrogen of the soybean, and bisphenol A (BPA) is a synthetic chemical used in the production of polycarbonate plastics. Both genistein and BPA disrupt the endocrine system in vivo and in vitro. Growing concerns of altered xenobiotic metabolism due to concomitant exposures from soy milk in BPA-laden baby bottles has warranted the investigation of the glucuronidation rate of genistein in the absence and presence (25 μM) of BPA by human liver microsomes (HLM) and rat liver microsomes (RLM). HLM yield V(max) values of 0.93 ± 0.10 nmol · min(-1) · mg(-1) and 0.62 ± 0.05 nmol · min(-1) · mg(-1) in the absence and presence of BPA, respectively. K(m) values for genistein glucuronidation by HLM in the absence and presence of BPA are 15.1 ± 7.9 μM and 21.5 ± 7.7 μM, respectively, resulting in a K(i) value of 58.7 μM for BPA. Significantly reduced V(max) and unchanged K(m) in the presence of BPA in HLM are suggestive of noncompetitive inhibition. In RLM, the presence of BPA resulted in a K(i) of 35.7 μM, an insignificant change in V(max) (2.91 ± 0.26 nmol · min(-1) · mg(-1) and 3.05 ± 0.41 nmol · min(-1) · mg(-1) in the absence and presence of BPA, respectively), and an increase in apparent K(m) (49.4 ± 14 μM with no BPA and 84.0 ± 28 μM with BPA), indicative of competitive inhibition. These findings are significant because they suggest that BPA is capable of inhibiting the glucuronidation of genistein in vitro, and that the type of inhibition is different between HLM and RLM.
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Project description:1. The amount and types of phospholipid and the fatty acid composition of the various phospholipids were examined in intact rat liver mitochondria, in mitochondria devoid of their outer membrane (preparation A) and in very small pieces derived from the disruption of the inner-membrane complexes (preparation B). The latter two preparations were obtained by digitonin treatment and carry out oxidative phosphorylation. 2. The ratio mug.atoms of phospholipid P/mg. of protein was 0.163 for intact mitochondria, decreased to 0.118 on removal of the outer membrane and increased markedly to 0.292 on disruption of the inner-membrane complex. 3. Examination of the various types of phospholipid present showed that the molar proportions cardiolipin:phosphatidylcholine:phosphatidylethanolamine were approx. 1:6:6 for intact mitochondria and 1:3:3 for preparations A and B. 4. There was a correlation between the recovery of cardiolipin and adenosine triphosphatase activity in the conversion of intact mitochondria into preparations A and B. 5. The fatty acid contents of the various types of phospholipid purified by thin-layer chromatography were identical in all three preparations. Our results show a considerably higher content of arachidonic acid and lower content of oleic acid for phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol than have previously been reported for mitochondrial phospholipids.
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